PROJECT SUMMARY ? Project 3 Currently, 2.8 million women in the United States with a personal history of breast cancer (PHBC) face years of imaging surveillance. Breast imaging surveillance is aimed at the early detection of second breast cancer events, either local recurrence or new cancers in the other breast, with the goal of decreasing breast cancer mortality. Treatment strategies for primary breast cancers routinely take into account women's clinical and tumor characteristics. However, unlike treatment guidelines, current surveillance guidelines recommend annual mammography for all women with a PHBC regardless of risk. With new information about tumor biology and emerging imaging technologies (digital breast tomosynthesis and breast MRI), we can move toward risk-based surveillance decision making by women and their physicians. Although new imaging methods show promise for screening, their ability to improve early second breast cancer detection and longer-term outcomes is not yet established. The overall goal of this project is to facilitate a shift from a single strategy of annual mammography for all women to individualized, risk-based strategies, incorporating the full range of available imaging modalities and reliable estimates of a woman's risk of surveillance outcomes. We propose to integrate women's risk factors and tumor characteristics to produce risk estimates for important surveillance mammography outcomes: benefits (early detection of second invasive breast cancer), failures (interval detection of second invasive breast cancer after negative mammography) and false alarms (false-positive recall or biopsy recommendations). Early evidence suggests that women's risk factors, primary breast cancer characteristics, age at diagnosis, mode of detection, and treatment choices can be used to identify women at high risk of surveillance mammography failure who might benefit from alternative surveillance strategies (tomosynthesis alone or mammography and MRI). In addition, women at low risk of surveillance failure could minimize their risk of false alarms by receiving mammography or tomosynthesis alone. Our scientific premise is that tailored strategies will improve surveillance outcomes by reducing both surveillance failures and false alarms compared with guideline-recommended annual mammography alone. Our specific aims are: Aim 1: Determine the benefits and harms of surveillance tomosynthesis compared with digital mammography among women with a PHBC. Aim 2: Develop novel risk prediction models to identify and directly compare a woman's cumulative absolute risk of surveillance mammography outcomes. Aim 3: Identify clinically actionable risk levels for consideration of more intensive surveillance, informed by perspectives of referring clinicians and radiologists. This project will combine clinical and imaging risk factors to estimate risks of important surveillance benefits, failures, and false alarms, supporting a shift away from a one size fits all annual surveillance strategy, toward individualized, risk-based strategies for women with a PHBC.